Abstract
The enzyme γ-glutamyl transferase (GGT) plays an important role in redox homeostasis and is overexpressed in many different cancers. The ability to assess GGT activity provides critical insights into cancer prognosis and pathology. Here, we present a novel imaging agent, ((15)N)(2)-DT-GG-PA, for in vivo assessment of GGT activity by hyperpolarized nitrogen-15 magnetic resonance imaging (HP (15)N MRI). This (15)N-labeled HP MRI probe is developed by introducing a long-lasting HP ((15)N)(2)-diazirine tag to deliver essential properties for in vivo detection of GGT activity. Our studies show a large chemical shift difference (Δδ = 6.3 ppm) between ((15)N)(2)-DT-GG-PA and its product, ((15)N)(2)-DT-PA, and long HP lifetimes of both compounds (T(1) = 196 and 81 s, respectively, at 1 T). We also demonstrate the in vivo feasibility of detecting GGT activity using HP ((15)N)(2)-DT-GG-PA in rat kidneys on a clinical 3 T MRI scanner. Finally, the success of ((15)N)(2)-DT-GG-PA highlights the transformative potential of the (15)N-tagging approach in designing novel HP (15)N MRI probes beyond structural restrictions for (15)N-isotope labeling.